The obtained results showed that all of curcumin, doxorubicin, and Dox-Cur treatments significantly decreased the viability, tumor spheroid formation, migration, and invasion in the GC model cells. Furthermore, apoptosis rates in AGS cells were increased in a concentration- and time-dependent manner in all of the treatment groups. Moreover, the anticancer activity of the Dox-Cur combination was significantly more than curcumin and doxorubicin treatments alone. According to the results, Dox-Cur combination therapy exerts more profound apoptotic and anticancer effects on the AGS cell line than curcumin or doxorubicin monotherapy. © 2020 Wiley Periodicals, Inc.. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.Nearly 350 million people worldwide are affected by a rare disease (RD) and ~80% of RDs have a genetic type, underscoring the need for access to reliable genomics education. Patient assistance in resource development can help ensure content is appropriate. The aim of this study was to define the needs and practical usage of the RD community to inform the scope and content of an online genetic course targeted toward the entire RD ecosystem. A high-level online survey (OS) was disseminated to 586 RD patients and family members/caregivers. A total of 251 individuals responded to the OS. Eight respondents were invited to participate in a follow-up focus group (FG). Nearly 87% of OS respondents have made efforts previously to learn more about genetics and 95.6% indicated a current interest in genetic education. Navigating healthcare systems, information sharing, and advocacy support were driving factors for this desire. Respondents indicated difficulty finding information on gene function, genetic testing, disease pathogenesis, and scientific advances. FG outcomes dove deeper into psychological needs including reducing emotional burden, alleviating fear of the unknown and seeking hope. Research identified high levels of interest in genetic education across all stages of the RD journey. Key themes identified in this study may help guide genetic counselors as they create their own patient and family-facing content. © 2020 National Society of Genetic Counselors.During neuronal activation, a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) occurs which is the basis of functional brain imaging with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Elevated intracranial pressure (eICP) has been shown to impair functional deoxy-Hb changes. This study investigated this effect and its relation to the underlying neuronal activity in the human primary somatosensory cortex (SI). Functional near-infrared spectroscopy (fNIRS) during somatosensory evoked potentials (SEP) monitoring was performed on 75 subjects during conditions of median nerve stimulation (MNS) and resting state, combined with normal breathing (NB) and eICP by escalating breathing maneuvers (breath holding [BH], Valsalva maneuver with 15?mmHg [V15] and 35?mmHg expiratory pressure [V35]). During NB, fNIRS revealed a typical oxygenated hemoglobin concentration (oxy-Hb) increase with deoxy-Hb decrease during MNS enabling SI brain mapping. Breathing maneuvers associated eICP produced a known global change of oxy-Hb and deoxy-Hb with and without MNS. When subtracting measurements during resting state from measurements during MNS, neither functional oxy-Hb nor deoxy-Hb changes could be recovered while SEPs remained unchanged. In conclusion, Valsalva-induced eICP prevents oxy-Hb and deoxy-Hb changes during neuronal activation in SI. This finding raises questions on the validity of oxy-Hb- and deoxy-Hb-based brain imaging (e.g., BOLD-fMRI) during eICP. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of the mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular-targeting drug delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multi-functional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli-responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this review, we surveyed the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria-targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondria-targeting nanotherapeutics. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.The biochemical functions of proteins are activated at the protein glass transition temperature, which has been proposed to be dependent upon protein-water interactions. However, at the molecular level it is unclear how ligand binding to well-defined binding sites can influence this transition temperature. We thus report molecular dynamics (MD) simulations of the ε subunit from thermophilic Bacillus PS3 in the ATP-free and ligand-bound states over a range of temperatures from 20 to 300 K, to study the influence of ligand association upon the transition temperature. We also measure the protein mean square displacement (MSD) in each state, which is well established as a means to quantify this dynamical temperature dependence. We find that the transition temperature is largely unaffected by ligand association, but the MSD beyond the transition temperature increases more rapidly in the ATP-free state. Our data suggests that ligands can effectively "shield" a binding site from solvent, and hence stabilize protein domains with increasing temperature. https://www.selleckchem.com/products/ms4078.html © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.